Black cohosh (Cimicifuga racemosa), is a widely used herbal medicine which is often assumed to be a safe and effective natural remedy for menopausal symptoms in women who have been advised by their doctors to avoid hormone replacement therapy (HRT) because they are at high risk for breast cancer or to discontinue HRT because they have been diagnosed with breast cancer. Some vendors of this herb advise that black cohosh "may help" breast cancer. This herb is widely used by breast cancer patients while they are receiving chemotherapy and radiation therapy. Studies in our laboratory showed that three commercially available black cohosh extracts significantly increase the response of breast cancer cells in cell culture to Adriamycin. Further tests with one of these extracts showed moderate sensitization to Taxotere, slight protection from Cisplatin, and no discernable effect on radiosensitivity. The goal of this project is to examine the therapeutic implications of these findings. A well characterized transplantable syngeneic tumor host system, the EMT6 mouse mammary carcinoma growing in SPF BALB/c Rw mice, will be used to study the effect of black cohosh on the response of tumors and normal tissues in vivo to cancer therapy. Effects on tumors will be assessed using quantitative experiments in which the growth of control tumors, tumors treated with drug alone, and tumors treated with black cohosh plus drug is measured and compared. We will also examine the effects of these treatments on the survival of the progenitor cells (CFU-GM/MK) of the bone marrow, a tissue which limits the intensity of cancer chemotherapy. Another series of studies will examine the effect of black cohosh extracts on the toxicity of Adriamycin, Taxotere, Cisplatin and radiation to human breast cancer cells in cell culture. These studies will assess whether the effects seen in mouse cells also occur in human cells. Data from our past studies suggest that this herb could change the effectiveness of standard cancer chemotherapeutic agents in treating cancer and could alter the toxicities of these drugs. This project will assess these possibilities. The findings will show whether this herb is inactive and harmless, potentially dangerous to breast cancer patients, or of potential value in the treatment of this disease.